Investigation and elimination of noncovalent artificial aggregates during non-reduced capillary electrophoresis-sodium dodecyl sulfate analysis of a multi-specific antibody.

Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) is widely used in the biopharmaceutical industry for monitoring purity and analyzing impurities. The accuracy of the method may be compromised by artificial species resulting from sample preparation or electrophoresis separation due to suboptimal conditions. During non-reduced CE-SDS analysis of a multispecific antibody (msAb), named as multispecific antibody C (msAb-C), a cluster of unexpected peaks was observed after the main peak.

The association of HLA-DRB1 allele group but not HLA-B or ERAP1-rs7063 gene polymorphisms with atopic dermatitis.

Atopic dermatitis (AD) is one of the most common dermatoses. According to current data 2.6 % of the world's population suffer from AD.

Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models.

How I diagnose and treat systemic mastocytosis with an associated hematologic neoplasm.

Over the last decade significant advances have been made by honing in on the diagnostic evaluation and the significance of molecular profiles in patients with systemic mastocytosis (SM), non-advanced and advanced.This is reflected in the 2022 iterations of the World Health Organization Edition 5 and International Consensus Criteria classifications.The impact of targeted KIT inhibitor therapies on patients treated within global trials has demonstrated significant improvements in the prognosis and overall survival for patients, leading to a change the treatment paradigm.

How I Treat Higher-Risk MDS.

Myelodysplastic syndromes/neoplasms (MDS) are a widely heterogenous group of myeloid malignancies characterized by morphologic dysplasia, a defective hematopoiesis, and recurrent genetic abnormalities. The original and revised International Prognostic Scoring Systems (IPSS) have been used to risk-stratify patients with MDS to guide treatment strategies. In higher-risk MDS, the therapeutic approach is geared toward delaying leukemic transformation and prolonging survival.

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.

Impact of Psychological Factors on Survival in Metastatic Esophagogastric Cancer: Secondary Analysis of a Randomized Controlled Trial.

Purpose: Early interdisciplinary supportive care (ESC), including psychological interventions, can improve the survival of patients with metastatic esophagogastric cancer (EGC). The purpose of the study was to evaluate the association between psychological factors and survival in patients with metastatic EGC.

Methods: A secondary analysis was conducted for an open-label randomized controlled trial of ESC, in which 246 patients with EGC completed a distress measure (the distress thermometer) and a depression symptom measure (the Patient Health Questionnaire-9 [PHQ-9]) at baseline before cancer treatments.

Validation of Clinical Dynamic Contrast-Enhanced Magnetic Resonance Imaging Perfusion Modeling and Neoadjuvant Chemotherapy Response Prediction in Breast Cancer Using FDG and Cu-DOTA-Trastuzumab Positron Emission Tomography Studies.

Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.

Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Assessing Functional Outcomes in the Pediatric Neurocritical Care Population after Discharge: A Pilot Study.

Objectives: Pediatric neurocritical care (PNCC) patients experience high rates of morbidity, but comprehensive follow-up is not universal. We sought to identify predictors of functional decline in these children to guide future resource allocation.

Patients And Methods: We conducted a prospective observational study in a quaternary children's hospital pediatric intensive care unit (PICU) from July 2023 to December 2023.

Screening for anxiety in patients with cancer: Diagnostic accuracy of GAD-7 items considering lowered GAD-7 cut-offs.

Background: A standard questionnaire for generalized anxiety disorders is the GAD-7. Attempts to improve its screening capacity in oncological settings resulted in a discussion about lowering its cut-off. This study examines the diagnostic accuracy of the GAD-7 items depending on applied cut-offs and whether, similar to depressive symptoms, a distinction between somatic-emotional and cognitive items might be relevant.

ADARp110 promotes hepatocellular carcinoma progression via stabilization of CD24 mRNA.

ADAR is highly expressed and correlated with poor prognosis in hepatocellular carcinoma (HCC), yet the role of its constitutive isoform ADARp110 in tumorigenesis remains elusive. We investigated the role of ADARp110 in HCC and underlying mechanisms using clinical samples, a hepatocyte-specific knock-in mouse model, and engineered cell lines. ADARp110 is overexpressed and associated with poor survival in both human and mouse HCC.

Patients' attitudes toward artificial intelligence (AI) in cancer care: A scoping review protocol.

Background: Artificial intelligence broadly refers to computer systems that simulate intelligent behaviour with minimal human intervention. Emphasizing patient-centered care, research has explored patients' perspectives on artificial intelligence in medical care, indicating general acceptance of the technology but also concerns about supervision. However, these views have not been systematically examined from the perspective of patients with cancer, whose opinions may differ given the distinct psychosocial toll of the disease.

Vitamin D, acute respiratory infections, and Covid-19: The curse of small-size randomised trials. A critical review with meta-analysis of randomised trials.

Background: Randomised trials conducted from 2006 to 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, larger randomised trials published in 2022 did not confirm the health benefits of VDS in COVID-19 patients.

Objective: To examine through a systematic review with meta-analysis the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and of randomised trials on VDS for the prevention of ARI.

Stereotactic Radiosurgery for World Health Organization Grade 2 and 3 Oligodendroglioma: An International Multicenter Study.

Background And Objectives: Oligodendrogliomas are primary brain tumors classified as isocitrate deshydrogenase-mutant and 1p19q codeleted in the 2021 World Health Organization Classification of central nervous system tumors. Surgical resection, radiotherapy, and chemotherapy are well-established management options for these tumors. Few studies have evaluated the efficacy of stereotactic radiosurgery (SRS) for oligodendroglioma.

Molecular and clinical traits of HER2-low breast cancer patients and their relationship with neoadjuvant treatment effectiveness.

Background: We aimed to investigate the clinical and molecular characteristics of different degrees of human epidermal growth factor receptor 2 (HER2) protein expression in HER2-negative breast cancer and the related factors affecting the efficacy of neoadjuvant chemotherapy in HER2-low breast cancer patients.

Methods: The study endpoint was pathological complete remission (PCR). Blood specimens and fresh cancer tissue samples were collected before neoadjuvant chemotherapy for whole-exon sequencing (WES) and RNA sequencing (RNA-seq), and patients were divided into a human epidermal growth factor receptor 2 (HER2)-low group and a HER2-0 group according to their HER2 expression status via bioinformatics analysis.

Metastatic Lung Lesion Changes in Follow-up Chest CT: The Advantage of Deep Learning Simultaneous Analysis of Prior and Current Scans With SimU-Net.

Purpose: Radiological follow-up of oncology patients requires the detection of metastatic lung lesions and the quantitative analysis of their changes in longitudinal imaging studies. Our aim was to evaluate SimU-Net, a novel deep learning method for the automatic analysis of metastatic lung lesions and their temporal changes in pairs of chest CT scans.

Materials And Methods: SimU-Net is a simultaneous multichannel 3D U-Net model trained on pairs of registered prior and current scans of a patient.

Identification and validation of mitochondria-related LncRNA signatures as a novel prognostic model for glioma.

A predictive model for long-term survival is needed, and mitochondrial dysfunction is a key feature of cancer metabolism, though its link to glioma is not well understood. The aim of this study was to identify the molecular characteristics associated with glioma prognosis and explore its potential function. We analyzed RNA-seq data from The Cancer Genome Atlas and identified differentially expressed mitochondrial long noncoding RNAs (lncRNAs) using R's 'limma' package.

Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

FDA Approval Summary: Tovorafenib for Relapsed or Refractory BRAF-altered Pediatric Low-Grade Glioma.

On April 23, 2024, FDA granted accelerated approval to tovorafenib, a type II RAF kinase inhibitor, for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Efficacy was evaluated in FIREFLY-1 (NCT04775485), a single-arm, open-label, multicenter trial that enrolled patients 6 months to 25 years of age with relapsed or refractory pLGG with an activating BRAF alteration who had received prior systemic therapy. The major efficacy outcome measure was radiologic overall response rate (ORR), defined as the proportion of patients with complete response, partial response, or minor response as determined by blinded independent central review using Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.

TRAIL agonists rescue mice from radiation-induced lung, skin or esophageal injury.

Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.

An Activin Receptor-Like Kinase 1-governed monocytic lineage shapes an immunosuppressive landscape in breast cancer metastases.

The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.

LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models.

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice.

A Proposed mHealth Intervention to Address Patient Barriers to Colposcopy Attendance: Qualitative Interview Study of Clinic Staff and Patient Perspectives.

Background: Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance.